A group of 9-aminoalkylfluorenes recently has been disclosed as having valuable antiarrhythmic activity; see U.S. Pat. Nos. 4,197,313 and 4,277,495. The 9-carbamoyl-9-aminoalkylfluorenes are among the most interesting compounds, and one compound within this group, namely 9-carbamoyl-9-(3-isopropylaminopropyl)fluorene, is now known generically as indecainide.
Lavagnino et al., in U.S. Pat. No. 4,282,170, disclose a process for preparing 9-carbamoyl-9-(3-aminopropyl)fluorene, an intermediate in a synthesis of indecainide, which process comprises hydrogenation of 9-carbamoyl-9-(2-cyanoethyl)fluorene. The hydrogenation reaction is said to be best carried out in an acidic medium, most preferably in glacial acetic acid, although organic solvents such as ethanol can be employed if desired.
We have now discovered that the hydrogenation process described in U.S. Pat. No. 4,282,170 leads to formation of observable quantities of fluorene dimer and trimer by-products, compounds of the formulas ##STR1## Removal of these by-products has proved extremely difficult, and in general they are carried through subsequent reactions and can be found in the final product.
An object of this invention is to provide an improvement in the process for hydrogenating 9-carbamoyl-9-(2-cyanoethyl)fluorene. The improvement provided by this invention results in reduced amounts of the aforementioned fluorene dimer and trimer by-products being produced, and thereby permits formation of a purer pharmaceutical agent.